{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T14:17:29Z","timestamp":1773411449958,"version":"3.50.1"},"reference-count":28,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2004]]},"abstract":"<i>Background:<\/i> At least half of all cases of early onset (<60) familial Alzheimer\u2019s disease (FAD) are caused by any of over 150 mutations in three genes: the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death. <i>Objective:<\/i> We investigated the effects of hypocapnia, a risk factor for both cognitive and neurodevelopment deficits, on caspase-3 activation, apoptosis, and amyloid \u03b2-protein (A\u03b2) production, and assessed the influence of the PS1\u03949 FAD mutation on these effects. <i>Method:<\/i> For this purpose, we exposed stably transfected H4 human neuroglioma cells to conditions consistent with hypocapnia (PCO<sub>2<\/sub> <40 mm Hg) and hypocapnia plus hypoxia (PO<sub>2<\/sub> <21%). <i>Results:<\/i> Hypocapnia (20 mm Hg CO<sub>2<\/sub> for 6 h) induced caspase-3 activation and apoptosis; the PS1\u03949 FAD mutation significantly potentiated these effects. Moreover, the combination of hypocapnia (20 mm Hg CO<sub>2<\/sub>) and hypoxia (5%O<sub>2<\/sub>) induced caspase-3 activation and apoptosis in a synergistic manner. Hypocapnia (5 and 20 mm Hg CO<sub>2 <\/sub>for 6 h) also led to an increased A\u03b2 production. <i>Conclusion:<\/i> The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis.<\/jats:p>","DOI":"10.1159\/000076667","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T06:15:27Z","timestamp":1081836927000},"page":"29-37","source":"Crossref","is-referenced-by-count":29,"title":["Hypocapnia Induces Caspase-3 Activation and Increases A\u03b2 Production"],"prefix":"10.1159","volume":"1","author":[{"given":"Zhongcong","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Moir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna M.","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Tesco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora M.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2004,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2FS0896-6273%2801%2900476-7"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2980748-5"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.274.33.23426"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0997-954"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.277.5324.373"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.272.33.20655"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1651-2227.1987.tb10488.x"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1093%2Fbja%2F40.12.920"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJMra012457"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1203%2F00006450-199707000-00005"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1203%2F00006450-200007000-00007"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1471-4159.1999.0732278.x"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038%2Fng0892-345"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1007%2Fs004150050640"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038%2F13518"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038%2F20446"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.277.5325.559"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1097%2F00004647-199704000-00002"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1471-4159.1999.0721019.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.273.51.33909"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1097%2F00001756-199612200-00074"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1006%2Fnbdi.2002.0542"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016%2FS0197-4580%2898%2900041-4"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-8993%2890%2991276-M"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016%2F0006-8993%2894%2990058-2"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.273.14.8217"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2980434-1"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.274.17.11549"}],"container-title":["Neurodegenerative Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/76667","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/76667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:13:25Z","timestamp":1745468005000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000076667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2004,4,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000076667","archive":["Portico"],"relation":{},"ISSN":["1660-2854","1660-2862"],"issn-type":[{"value":"1660-2854","type":"print"},{"value":"1660-2862","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004]]}}}